SAFETY OF PRESCRIPTION NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN ADULTS WITH INFLAMMATORY BOWEL DISEASE: DATA FROM A LARGE ADMINISTRATIVE COHORT

Abstract BACKGROUND The concern that nonsteroidal anti-inflammatory drugs (NSAIDs) may precipitate flares of inflammatory bowel disease (IBD) has limited their use in managing musculoskeletal symptoms in this population, but safety data are mixed. METHODS This was a retrospective cohort study of IBD patients from Optum’s de-identified Clinformatics Data Mart Database (2000-2022). Patients with a new NSAID prescription fill (“exposed”) were matched to those without an NSAID fill during the study period (“unexposed”) by age and calendar year when IBD criteria were met (Figure 1). The index date for exposed patients was date of first NSAID fill; unexposed patients were assigned a matched index date based on time from meeting IBD criteria. A propensity score was calculated to balance covariates across exposure groups. The primary outcome was IBD-related hospitalization, defined as any hospitalization >1 day duration with an IBD diagnosis code as the primary or secondary discharge code. Secondary outcomes included all-cause hospitalization and gastrointestinal surgery. Propensity score-based inverse probability of treatment weighted (IPTW) Cox proportional hazards models evaluated the association between NSAID exposure and time to each outcome across IBD subtypes. A hazard ratio (HR) of 1.2 was set as the pre-specified non-inferiority margin based on discussions with IBD content experts. RESULTS Among 271,236 patients with IBD, 29.7% were NSAID exposed. All covariates were balanced across groups after IPTW. In the IPTW-weighted Cox model, NSAID exposure was associated with a small increase in IBD-related hospitalization in the overall IBD cohort (HR 1.08, 95% CI 1.05-1.11; Figure 2) but demonstrated non-inferiority. Exposed patients experienced an adjusted 0.06 IBD-related hospitalizations/person-year versus 0.05 events/person-year in the unexposed group (absolute risk difference 0.007, number needed to harm 137). No significant increase in IBD-related hospitalization was seen in the ulcerative colitis subgroup (HR 0.96, 95% CI 0.91-1.01), but there was a significant increase in those with Crohn’s disease (HR 1.16, 95% CI 1.11-1.21), with non-inferiority not met. There were significantly higher rates of gastrointestinal surgery (overall HR 1.23, 95% CI 1.19-1.28) and all-cause hospitalization (overall HR 1.30, 95% CI 1.28-1.32) with neither meeting non-inferiority. CONCLUSION Prescription NSAID exposure was associated with a numerically small risk of IBD-related hospitalization below the pre-specified non-inferiority threshold. Risk was not seen in patients with ulcerative colitis, while small magnitude risks were present in those with Crohn’s disease. These results challenge the current paradigm of avoiding NSAIDs in all patients with IBD and suggest that NSAID risks may be acceptable for many patients with significant joint disease.